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UNIT I:
Protein Structure
and Function
1
Amino Acids
I. OVERVIEW
Proteins are the most abundant and functionally diverse molecules in
living systems. Virtually every life process depends on this class of
molecules. For example, enzymes and polypeptide hormones direct and
regulate metabolism in the body, whereas contractile proteins in muscle
permit movement. In bone, the protein collagen forms a framework for
the deposition of calcium phosphate crystals, acting like the steel
cables in reinforced concrete. In the bloodstream, proteins, such as
hemoglobin and plasma albumin, shuttle molecules essential to life,
whereas immunoglobulins fight infectious bacteria and viruses. In short,
proteins display an incredible diversity of functions, yet all share the
common structural feature of being linear polymers of amino acids. This
chapter describes the properties of amino acids. Chapter 2 explores
how these simple building blocks are joined to form proteins that have
unique three-dimensional structures, making them capable of performing specific biologic functions.
II. STRUCTURE OF THE AMINO ACIDS
Although more than 300 different amino acids have been described in
nature, only 20 are commonly found as constituents of mammalian proteins. [Note: These are the only amino acids that are coded for by DNA,
the genetic material in the cell (see p. 395).] Each amino acid (except
for proline, which has a secondary amino group) has a carboxyl group,
a primary amino group, and a distinctive side chain (“R-group”) bonded
to the α-carbon atom (Figure 1.1A). At physiologic pH (approximately
pH 7.4), the carboxyl group is dissociated, forming the negatively
charged carboxylate ion (– COO–), and the amino group is protonated
(– NH3+). In proteins, almost all of these carboxyl and amino groups are
combined through peptide linkage and, in general, are not available for
chemical reaction except for hydrogen bond formation (Figure 1.1B).
Thus, it is the nature of the side chains that ultimately dictates the role
A
Free amino acid
Common to all α-amino
acids of proteins
C OH
CO
COOH
+H N
3
Cα H
R
Amino
group
Side chain
is distinctive
for each amino
acid.
Carboxyl
group
α-Carbon is
between the
carboxyl and the
amino groups.
Amino acids combined
B through
peptide linkages
NH-CH-CO-NH-CH-CO
R
R
Side chains determine
properties of proteins.
Figure 1.1
Structural features of amino acids
(shown in their fully protonated form).
1
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1. Amino Acids
an amino acid plays in a protein. It is, therefore, useful to classify the
amino acids according to the properties of their side chains, that is,
whether they are nonpolar (have an even distribution of electrons) or
polar (have an uneven distribution of electrons, such as acids and
bases; Figures 1.2 and 1.3).
A. Amino acids with nonpolar side chains
Each of these amino acids has a nonpolar side chain that does not
gain or lose protons or participate in hydrogen or ionic bonds
(Figure 1.2). The side chains of these amino acids can be thought of
as “oily” or lipid-like, a property that promotes hydrophobic interactions (see Figure 2.10, p. 19).
1. Location of nonpolar amino acids in proteins: In proteins found in
aqueous solutions––a polar environment––the side chains of the
nonpolar amino acids tend to cluster together in the interior of the
protein (Figure 1.4). This phenomenon, known as the hydrophobic
NONPOLAR SIDE CHAINS
COOH
+H N
3
C
H
+H
3N C
H
H
Glycine
H
CH2
C
H3C
CH
CH3
C
H
H
C
CH3
Leucine
H3N C H
COOH
+H
3N
H
CH2
CH3
Isoleucine
Phenylalanine
COOH
+H N
3
C
COOH
H
CH2
CH2
+H N
2
C
CH2
H2C
CH
S
Tryptophan
C
CH2
COOH
+
H
Valine
COOH
+H N
3
CH
H3C
CH3
N
H
3N
Alanine
COOH
C
+H
CH3
pK2 = 9.6
+H N
3
COOH
COOH
pK1 = 2.3
C
CH2
CH2
H
CH3
Methionine
Proline
Figure 1.2
Classification of the 20 amino acids commonly found in proteins, according to the charge and polarity of their
side chains at acidic pH is shown here and continues in Figure 1.3. Each amino acid is shown in its fully protonated
form, with dissociable hydrogen ions represented in red print. The pK values for the α-carboxyl and α-amino
groups of the nonpolar amino acids are similar to those shown for glycine. (Continued in Figure 1.3.)
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II. Structure of the Amino Acids
3
UNCHARGED POLAR SIDE CHAINS
pK1 = 2.2
COOH
+H N
3
COOH
+H N
3
C
H
H
C
OH
+H N
3
C
H
H
C
OH
H
C
OH
pK3 = 10.1
Tyrosine
COOH
+H N
3
H
C
CH2
C
CH2
NH2
COOH
H
CH2
O
CH2
Threonine
COOH
H
pK2 = 9.1
CH3
Serine
+H N
3
C
COOH
+H N
3
Asparagine
H
CH2
pK3 = 10.8
C
O
C
pK1 = 1.7
SH
pK2 = 8.3
NH2
Glutamine
Cysteine
ACIDIC SIDE CHAINS
pK1 = 2.1
COOH
+H
pK3 = 9.8
3N
C
COOH
pK3 = 9.7
H
+H
3N
H
CH2
CH2
C
O
C
CH2
OH
pK2 = 3.9
C
O
OH
pK2 = 4.3
Aspartic acid
BASIC SIDE CHAINS
pK1 = 2.2
pK1 = 1.8
pK3 = 9.2
pK2 = 9.2
COOH
+H N
3
C
+H
H
CH2
C
+HN
C
H
pK2 = 6.0
pK2 = 9.0
COOH
3N C
+H
H
3N
COOH
C
CH2
CH2
CH
CH2
CH2
NH
CH2
CH2
CH2
NH3+
N
pK3 = 10.5
H
H
C NH2+
pK3 = 12.5
NH2
Histidine
Lysine
Arginine
Figure 1.3
Classification of the 20 amino acids commonly found in proteins, according to the charge and polarity
of their side chains at acidic pH (continued from Figure 1.2).
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1. Amino Acids
Nonpolar amino
acids ( ) cluster
in the interior of
soluble proteins.
Nonpolar amino
acids ( ) cluster
on the surface of
membrane proteins.
Cell
membrane
Polar amino acids
( ) cluster on
the surface of
soluble proteins.
Soluble protein
Membrane protein
Figure 1.4
Location of nonpolar amino acids
in soluble and membrane proteins.
Secondary amino
group
Primary amino
group
COOH
+H N
2
H2C
C
COOH
H
+H N
3
CH2
C
H
CH3
CH2
Alanine
Proline
Figure 1.5
Comparison of the secondary
amino group found in proline with
the primary amino group found
in other amino acids, such as
alanine.
+H N
3
COOH
C H
CH2
effect, is the result of the hydrophobicity of the nonpolar R-groups,
which act much like droplets of oil that coalesce in an aqueous
environment. The nonpolar R-groups thus fill up the interior of the
folded protein and help give it its three-dimensional shape.
However, for proteins that are located in a hydrophobic environment, such as a membrane, the nonpolar R-groups are found on
the outside surface of the protein, interacting with the lipid environment (see Figure 1.4). The importance of these hydrophobic
interactions in stabilizing protein structure is discussed on p. 19.
Sickle cell anemia, a sickling disease of red
blood cells, results from the substitution of polar
glutamate by nonpolar valine at the sixth position
in the β subunit of hemoglobin (see p. 36).
2. Proline: Proline differs from other amino acids in that proline’s
side chain and α-amino N form a rigid, five-membered ring structure (Figure 1.5). Proline, then, has a secondary (rather than a primary) amino group. It is frequently referred to as an imino acid.
The unique geometry of proline contributes to the formation of the
fibrous structure of collagen (see p. 45), and often interrupts the
α-helices found in globular proteins (see p. 26).
B. Amino acids with uncharged polar side chains
These amino acids have zero net charge at neutral pH, although the
side chains of cysteine and tyrosine can lose a proton at an alkaline
pH (see Figure 1.3). Serine, threonine, and tyrosine each contain a
polar hydroxyl group that can participate in hydrogen bond formation
(Figure 1.6). The side chains of asparagine and glutamine each
contain a carbonyl group and an amide group, both of which can
also participate in hydrogen bonds.
1. Disulfide bond: The side chain of cysteine contains a sulfhydryl
group (–SH), which is an important component of the active site
of many enzymes. In proteins, the –SH groups of two cysteines
can become oxidized to form a dimer, cystine, which contains a
covalent cross-link called a disulfide bond (–S–S–). (See p. 19 for
a further discussion of disulfide bond formation.)
Tyrosine
O
H
Carbonyl O
group C
Hydrogen
bond
Many extracellular proteins are stabilized by
disulfide bonds. Albumin, a blood protein that
functions as a transpor ter for a variety of
molecules, is an example.
2. Side chains as sites of attachment for other compounds: The
Figure 1.6
Hydrogen bond between the
phenolic hydroxyl group of tyrosine
and another molecule containing a
carbonyl group.
polar hydroxyl group of serine, threonine, and, rarely, tyrosine, can
serve as a site of attachment for structures such as a phosphate
group. In addition, the amide group of asparagine, as well as the
hydroxyl group of serine or threonine, can serve as a site of attachment for oligosaccharide chains in glycoproteins (see p. 165).
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II. Structure of the Amino Acids
C. Amino acids with acidic side chains
The amino acids aspartic and glutamic acid are proton donors. At
physiologic pH, the side chains of these amino acids are fully ionized,
containing a negatively charged carboxylate group (–COO–). They are,
therefore, called aspartate or glutamate to emphasize that these amino
acids are negatively charged at physiologic pH (see Figure 1.3).
D. Amino acids with basic side chains
The side chains of the basic amino acids accept protons (see Figure
1.3). At physiologic pH the side chains of lysine and arginine are fully
ionized and positively charged. In contrast, histidine is weakly basic,
and the free amino acid is largely uncharged at physiologic pH.
However, when histidine is incorporated into a protein, its side chain
can be either positively charged or neutral, depending on the ionic
environment provided by the polypeptide chains of the protein. This
is an important property of histidine that contributes to the role it
plays in the functioning of proteins such as hemoglobin (see p. 31).
E. Abbreviations and symbols for commonly occurring amino acids
Each amino acid name has an associated three-letter abbreviation
and a one-letter symbol (Figure 1.7). The one-letter codes are determined by the following rules:
1. Unique first letter: If only one amino acid begins with a particular
letter, then that letter is used as its symbol. For example, I =
isoleucine.
2. Most commonly occurring amino acids have priority: If more
than one amino acid begins with a particular letter, the most common of these amino acids receives this letter as its symbol. For
example, glycine is more common than glutamate, so G = glycine.
3. Similar sounding names: Some one-letter symbols sound like the
amino acid they represent. For example, F = phenylalanine, or W
= tryptophan (“twyptophan” as Elmer Fudd would say).
4. Letter close to initial letter: For the remaining amino acids, a one-
letter symbol is assigned that is as close in the alphabet as possible to the initial letter of the amino acid, for example, K = lysine.
Furthermore, B is assigned to Asx, signifying either aspartic acid
or asparagine, Z is assigned to Glx, signifying either glutamic acid
or glutamine, and X is assigned to an unidentified amino acid.
F. Optical properties of amino acids
The α-carbon of an amino acid is attached to four different chemical
groups and is, therefore, a chiral or optically active carbon atom.
Glycine is the exception because its α-carbon has two hydrogen
substituents and, therefore, is optically inactive. Amino acids that
have an asymmetric center at the α-carbon can exist in two forms,
designated D and L, that are mirror images of each other (Figure
1.8). The two forms in each pair are termed stereoisomers, optical
isomers, or enantiomers. All amino acids found in proteins are of the
L-configuration. However, D-amino acids are found in some antibiotics and in plant and bacterial cell walls. (See p. 253 for a discussion of D-amino acid metabolism.)
5
1
Unique first letter:
Cysteine
Histidine
Isoleucine
Methionine
Serine
Valine
2
C
H
I
=
=
=
=
=
=
M
S
V
=
=
=
=
=
Ala
Gly
Leu
Pro
Thr
A
=
=
=
=
=
G
L
P
T
Similar sounding names:
Arginine
Asparagine
Aspartate
Glutamate
Glutamine
Phenylalanine
Tyrosine
Tryptophan
4
Cys
His
Ile
Met
Ser
Val
Most commonly occurring
amino acids have priority:
Alanine
Glycine
Leucine
Proline
Threonine
3
=
=
=
=
=
=
=
=
=
=
=
=
=
=
Arg
Asn
Asp
Glu
Gln
Phe
Tyr
Trp
=
=
=
=
=
=
=
=
R
N
D
E
(“aRginine”)
(contains N)
("asparDic")
("glutEmate")
Q (“Q-tamine”)
F (“Fenylalanine”)
Y (“tYrosine”)
W (double ring in
the molecule)
Letter close to initial letter:
Aspartate or
asparagine
Glutamate or
glutamine
Lysine
Undetermined
amino acid
=
Asx =
B (near A)
=
Glx =
Z
=
=
Lys =
K (near L)
X
Figure 1.7
Abbreviations and symbols for the
commonly occurring amino acids.
OH
CO
H
C
+H3N
CH3
e
nin
-Ala
L
HO
OC
H C
N
H C H3+
3
D-A
lan
ine
Figure 1.8
D and L forms of alanine
are mirror images.
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1. Amino Acids
III. ACIDIC AND BASIC PROPERTIES OF AMINO ACIDS
Amino acids in aqueous solution contain weakly acidic α-carboxyl
groups and weakly basic α-amino groups. In addition, each of the acidic
and basic amino acids contains an ionizable group in its side chain.
Thus, both free amino acids and some amino acids combined in
peptide linkages can act as buffers. Recall that acids may be defined as
proton donors and bases as proton acceptors. Acids (or bases)
described as “weak” ionize to only a limited extent. The concentration of
protons in aqueous solution is expressed as pH, where pH = log 1/[H+]
or –log [H+]. The quantitative relationship between the pH of the solution and concentration of a weak acid (HA) and its conjugate base (A–)
is described by the Henderson-Hasselbalch equation.
OH–
H20
CH3COOH
A. Derivation of the equation
FORM I
(acetic acid, HA)
FORM II
H+ (acetate, A– )
Buffer region
[II] > [I]
1.0
Equivalents OH– added
Consider the release of a proton by a weak acid represented by HA:
CH3COO–
[I] = [II]
HA
weak
acid
Ka
pKa = 4.8
[I] > [II]
0
3
4
5
6
pH
Figure 1.9
Titration curve of acetic acid.
H+
proton
7
A–
salt form
or conjugate base
+
The “salt” or conjugate base, A–, is the ionized form of a weak acid.
By definition, the dissociation constant of the acid, Ka, is
0.5
0
→
←
[H+] [A–]
[HA]
[Note: The larger the Ka, the stronger the acid, because most of the
HA has dissociated into H+ and A–. Conversely, the smaller the Ka,
the less acid has dissociated and, therefore, the weaker the acid.]
By solving for the [H+] in the above equation, taking the logarithm of
both sides of the equation, multiplying both sides of the equation by
–1, and substituting pH = – log [H+ ] and pKa = – log Ka, we obtain
the Henderson-Hasselbalch equation:
pH
pKa + log
[A– ]
[HA]
B. Buffers
A buffer is a solution that resists change in pH following the addition of
an acid or base. A buffer can be created by mixing a weak acid (HA) with
its conjugate base (A–). If an acid such as HCl is then added to such a
solution, A– can neutralize it, in the process being converted to HA. If a
base is added, HA can neutralize it, in the process being converted to
A–. Maximum buffering capacity occurs at a pH equal to the pKa, but a
conjugate acid/base pair can still serve as an effective buffer when the
pH of a solution is within approximately ±1 pH unit of the pKa. If the
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III. Acidic and Basic Properties of Amino Acids
OH–
7
OH–
H20
COOH
+H N C H
3
–
H20
COO
+H N C H
3
CH3
H+
FORM I
pK1 = 2.3
CH3
FORM II
–
COO
H2N C H
H+
pK2 = 9.1
CH3
FORM III
Alanine in acid solution
(pH less than 2)
Alanine in neutral solution
(pH approximately 6)
Alanine in basic solution
(pH greater than 10)
Net charge = +1
Net charge = 0
(isoelectric form)
Net charge = –1
Figure 1.10
Ionic forms of alanine in acidic, neutral, and basic solutions.
amounts of HA and A– are equal, the pH is equal to the pKa. As shown in
Figure 1.9, a solution containing acetic acid (HA = CH3 – COOH) and
acetate (A– = CH3 – COO–) with a pKa of 4.8 resists a change in pH from
pH 3.8 to 5.8, with maximum buffering at pH 4.8. At pH values less than
the pKa, the protonated acid form (CH3 – COOH) is the predominant
species. At pH values greater than the pKa, the deprotonated base form
(CH3 – COO–) is the predominant species in solution.
C. Titration of an amino acid
1. Dissociation of the carboxyl group: The titration curve of an
amino acid can be analyzed in the same way as described for
acetic acid. Consider alanine, for example, which contains both
an α-carboxyl and an α-amino group. At a low (acidic) pH, both of
these groups are protonated (shown in Figure 1.10). As the pH of
the solution is raised, the – COOH group of Form I can dissociate
by donating a proton to the medium. The release of a proton
results in the formation of the carboxylate group, – COO–. This
structure is shown as Form II, which is the dipolar form of the
molecule (see Figure 1.10). This form, also called a zwitterion, is
the isoelectric form of alanine, that is, it has an overall (net)
charge of zero.
2. Application of the Henderson-Hasselbalch equation: The dissoci-
ation constant of the carboxyl group of an amino acid is called K1,
rather than Ka, because the molecule contains a second titratable
group. The Henderson-Hasselbalch equation can be used to
analyze the dissociation of the carboxyl group of alanine in the
same way as described for acetic acid:
K1
[H+] [II]
[I]
where I is the fully protonated form of alanine, and II is the isoelectric form of alanine (see Figure 1.10). This equation can be
rearranged and converted to its logarithmic form to yield:
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1. Amino Acids
pH
pK1 + log
[II]
[I]
3. Dissociation of the amino group: The second titratable group of
COO
H2N C H
alanine is the amino (– NH3+) group shown in Figure 1.10. This is
a much weaker acid than the – COOH group and, therefore, has a
much smaller dissociation constant, K2. [Note: Its pKa is therefore
larger.] Release of a proton from the protonated amino group of
Form II results in the fully deprotonated form of alanine, Form III
(see Figure 1.10).
–
CH3
4. pKs of alanine: The sequential dissociation of protons from the
FORM III
Region of
buffering
Region of
buffering
[II] = [III]
Equivalents OH– added
2.0
pI = 5.7
1.5
1.0
5. Titration curve of alanine: By applying the Hender son-
[I] = [II]
pK
p
K2 = 9.
9.1
pK1 = 2.3
0.5
0
0
2
4
6
8
10
pH
p
COOH
+H N C H
3
CH3
carboxyl and amino groups of alanine is summarized in Figure
1.10. Each titratable group has a pKa that is numerically equal to
the pH at which exactly one half of the protons have been
removed from that group. The pK a for the most acidic group
(–COOH) is pK1, whereas the pKa for the next most acidic group
(– NH3+) is pK2.
COO
3N C H
–
+H
CH3
Hasselbalch equation to each dissociable acidic group, it is possible to calculate the complete titration curve of a weak acid. Figure
1.11 shows the change in pH that occurs during the addition of
base to the fully protonated form of alanine (I) to produce the
completely deprotonated form (III). Note the following:
a. Buffer pairs: The – COOH/– COO– pair can serve as a buffer in
the pH region around pK 1, and the – NH 3+/– NH 2 pair can
buffer in the region around pK2.
b. When pH = pK: When the pH is equal to pK 1 (2.3), equal
FORM II
amounts of Forms I and II of alanine exist in solution. When
the pH is equal to pK2 (9.1), equal amounts of Forms II and III
are present in solution.
Figure 1.11
The titration curve of alanine.
c. Isoelectric point: At neutral pH, alanine exists predominantly
FORM I
as the dipolar Form II in which the amino and carboxyl groups
are ionized, but the net charge is zero. The isoelectric point
(pI) is the pH at which an amino acid is electrically neutral, that
is, in which the sum of the positive charges equals the sum of
the negative charges. For an amino acid, such as alanine, that
has only two dissociable hydrogens (one from the α-carboxyl
and one from the α-amino group), the pI is the average of pK1
and pK2 (pI = [2.3 + 9.1]/2 = 5.7, see Figure 1.11). The pI is
thus midway between pK1 (2.3) and pK2 (9.1). pI corresponds
to the pH at which the Form II (with a net charge of zero) predominates, and at which there are also equal amounts of
Forms I (net charge of +1) and III (net charge of –1).
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III. Acidic and Basic Properties of Amino Acids
Separation of plasma proteins by charge typically
is done at a pH above the pI of the major proteins, thus, the charge on the proteins is negative.
In an electric field, the proteins will move toward
the positive electrode at a rate determined by
their net negative charge. Variations in the mobility pattern are suggestive of certain diseases.
9
A
pH = pK + log
D. Other applications of the Henderson-Hasselbalch equation
The Henderson-Hasselbalch equation can be used to calculate how
the pH of a physiologic solution responds to changes in the concentration of a weak acid and/or its corresponding “salt” form. For example, in the bicarbonate buffer system, the Henderson-Hasselbalch
equation predicts how shifts in the bicarbonate ion concentration,
[HCO3–], and CO2 influence pH (Figure 1.12A). The equation is also
useful for calculating the abundance of ionic forms of acidic and
basic drugs. For example, most drugs are either weak acids or weak
bases (Figure 1.12B). Acidic drugs (HA) release a proton (H+), causing a charged anion (A–) to form.
→
←
HA
Pulmonary obstruction causes an
increase in carbon dioxide and
causes the pH to fall, resulting
in respiratory acidosis.
LUNG
ALVEOLI
CO2 + H2O
B
H2CO3
BH
→
←
H+ + HCO3-
DRUG ABSORPTION
–
pH = pK + log [Drug ]
[Drug-H]
At the pH of the stomach (1.5), a
drug like aspirin (weak acid,
pK = 3.5) will be largely protonated
(COOH) and, thus, uncharged.
Uncharged drugs generally cross
membranes more rapidly than
charged molecules.
STOMACH
H+ + A–
Weak bases (BH+) can also release a H+. However, the protonated
form of basic drugs is usually charged, and the loss of a proton produces the uncharged base (B).
+
[HCO3– ]
[CO2]
An increase in HCO3–
causes the pH to rise.
6. Net charge of amino acids at neutral pH: At physiologic pH,
amino acids have a negatively charged group (– COO–) and a
positively charged group (– NH3+), both attached to the α-carbon.
[Note: Glutamate, aspartate, histidine, arginine, and lysine have
additional potentially charged groups in their side chains.]
Substances, such as amino acids, that can act either as an acid
or a base are defined as amphoteric, and are referred to as
ampholytes (amphoteric electrolytes).
BICARBONATE AS A BUFFER
B+ H
+
A drug passes through membranes more readily if it is uncharged.
Thus, for a weak acid such as aspirin, the uncharged HA can permeate through membranes and A– cannot. For a weak base, such
as morphine, the uncharged form, B, penetrates through the cell
membrane and BH+ does not. Therefore, the effective concentration
of the permeable form of each drug at its absorption site is determined by the relative concentrations of the charged and uncharged
forms. The ratio between the two forms is determined by the pH at
the site of absorption, and by the strength of the weak acid or base,
which is represented by the pK a of the ionizable group. The
Henderson-Hasselbalch equation is useful in determining how much
drug is found on either side of a membrane that separates two compartments that differ in pH, for example, the stomach (pH 1.0–1.5)
and blood plasma (pH 7.4).
Lipid
membrane
H+
AH+
HA
H+
AH+
HA
LUMEN OF
STOMACH
BLOOD
Figure 1.12
The Henderson-Hasselbalch
equation is used to predict: A,
changes in pH as the concentrations
of HCO3– or CO2 are altered;
or B, the ionic forms of drugs.
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10
1. Amino Acids
A Linked concept boxes
Amino acids
(fully protonated)
can
Release H+
cross-linked
B Concepts
within a map
Degradation
of body
protein
is produced by
Simultaneous
synthesis and
degradation
Amino
acid
pool
Protein
turnover
leads to
IV. CONCEPT MAPS
Students sometimes view biochemistry as a blur of facts or equations to
be memorized, rather than a body of concepts to be understood. Details
provided to enrich understanding of these concepts inadvertently turn
into distractions. What seems to be missing is a road map—a guide that
provides the student with an intuitive understanding of how various topics fit together to make sense. The authors have, therefore, created a
series of biochemical concept maps to graphically illustrate relationships
between ideas presented in a chapter, and to show how the information
can be grouped or organized. A concept map is, thus, a tool for visualizing the connections between concepts. Material is represented in a hierarchic fashion, with the most inclusive, most general concepts at the top
of the map, and the more specific, less general concepts arranged
beneath. The concept maps ideally function as templates or guides for
organizing information, so the student can readily find the best ways to
integrate new information into knowledge they already possess.
A. How is a concept map constructed?
1. Concept boxes and links: Educators define concepts as “per-
Synthesis
of body
protein
is consumed by
Amino
acid
pool
C Concepts cross-linked
to other chapters and
to other books in the
Lippincott Series
. . . how the
protein folds
into its native
conformation
Structure
of Proteins
2
. . . how altered
protein folding
leads to prion
disease, such
as CreutzfeldtJakob disease
Lippincott's
Illustrated
Reviews
gy
o
l
io
b
ro
ic
M
Figure 1.13
Symbols used in concept maps.
ceived regularities in events or objects.” In our biochemical maps,
concepts include abstractions (for example, free energy), processes (for example, oxidative phosphorylation), and compounds
(for example, glucose 6-phosphate). These broadly defined concepts are prioritized with the central idea positioned at the top of
the page. The concepts that follow from this central idea are then
drawn in boxes (Figure 1.13A). The size of the type indicates the
relative importance of each idea. Lines are drawn between concept boxes to show which are related. The label on the line
defines the relationship between two concepts, so that it reads as
a valid statement, that is, the connection creates meaning. The
lines with arrowheads indicate in which direction the connection
should be read (Figure 1.14).
2. Cross-links: Unlike linear flow charts or outlines, concept maps
may contain cross-links that allow the reader to visualize complex
relationships between ideas represented in different parts of the
map (Figure 1.13B), or between the map and other chapters in
this book or companion books in the series (Figure 1.13C). Crosslinks can thus identify concepts that are central to more than one
discipline, empowering students to be effective in clinical situations, and on the United States Medical Licensure Examination
(USMLE) or other examinations, that bridge disciplinary boundaries. Students learn to visually perceive nonlinear relationships
between facts, in contrast to cross-referencing within linear text.
V. CHAPTER SUMMARY
Each amino acid has an α-carboxyl group and a primary α-amino
group (except for proline, which has a secondary amino group). At
physiologic pH, the α-carboxyl group is dissociated, forming the negatively charged carboxylate ion (– COO–), and the α-amino group is protonated (– NH3+). Each amino acid also contains one of 20 distinctive
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V. Chapter Summary
11
Amino acids
are composed of
α-Carboxyl group
(–COOH)
α-Amino group
(–NH2)
when protonated can
Side chains
(20 different ones)
Release H
+
and act as
is
is
Deprotonated (COO–)
at physiologic pH
Protonated (NH3+ )
at physiologic pH
Weak acids
grouped as
described by
Henderson-Hasselbalch
equation:
[A–]
pH = pKa + log
[HA]
Nonpolar
side chains
Alanine
Glycine
Isoleucine
Leucine
Methionine
Phenylalanine
Proline
Tryptophan
Valine
Uncharged polar
side chains
Asparagine
Cysteine
Glutamine
Serine
Threonine
Tyrosine
Acidic
side chains
Aspartic acid
Glutamic acid
characterized by
Side chain dissociates
to –COO– at
physiologic pH
Basic
side chains
predicts
Arginine
Histidine
Lysine
Buffering capacity
predicts
characterized by
Side chain is protonated and
generally has a
positive charge
at physiologic pH
Buffering occurs
±1 pH unit of pKa
predicts
found
found
found
found
Maximal buffer
when pH = pKa
On the outside of proteins that function in an aqueous environment
and in the interior of membrane-associated proteins
predicts
In the interior of proteins that function
in an aqueous environment and on
the surface of proteins (such as membrane
proteins) that interact with lipids
In proteins, most
α-COO– and
α-NH3+ of amino
acids are
combined through
peptide bonds.
Therefore, these
groups are not
available for
chemical reaction.
Figure 1.14
Key concept map for amino acids.
pH = pKa when [HA] = [A– ]
Thus, the chemical
nature of the side
chain determines
the role that the
amino acid plays
in a protein,
particularly . . .
Structure
of Proteins
. . . how the
protein folds
into its native
conformation.
2
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1. Amino Acids
side chains attached to the α-carbon atom. The chemical nature of this side chain determines the function of
an amino acid in a protein, and provides the basis for classification of the amino acids as nonpolar ,
uncharged polar, acidic, or basic. All free amino acids, plus charged amino acids in peptide chains, can serve
as buffers. The quantitative relationship between the pH of a solution and the concentration of a weak acid
(HA) and its conjugate base (A–) is described by the Henderson-Hasselbalch equation. Buffering occurs
within ±1pH unit of the pKa, and is maximal when pH = pKa, at which [A–] = [HA]. The α-carbon of each amino
acid (except glycine) is attached to four different chemical groups and is, therefore, a chiral or optically active
carbon atom. Only the L-form of amino acids is found in proteins synthesized by the human body.
Study Questions
Choose the ONE correct answer.
Equivalents OH– added
1.1 The letters A through E designate certain regions on
the titration curve for glycine (shown below). Which
one of the following statements concerning this curve
is correct?
E
2.0
D
1.5
1.0
C
0.5
B
A
0
0
2
4
6
8
Correct answer = C. C represents the isoelectric
point or pI, and as such is midway between pK1
and pK 2 for this monoamino monocarboxylic
acid. Glycine is fully protonated at Point A. Point
B represents a region of maximum buffering, as
does Point D. Point E represents the region
where glycine is fully deprotonated.
10
pH
A. Point A represents the region where glycine is
deprotonated.
B. Point B represents a region of minimal buffering.
C. Point C represents the region where the net charge
on glycine is zero.
D. Point D represents the pK of glycine’s carboxyl
group.
E. Point E represents the pI for glycine.
1.2 Which one of the following statements concerning the
peptide shown below is correct?
Gly-Cys-Glu-Ser-Asp-Arg-Cys
A. The peptide contains glutamine.
B. The peptide contains a side chain with a secondary
amino group.
C. The peptide contains a majority of amino acids with
side chains that would be positively charged at pH 7.
D. The peptide is able to form an internal disulfide
bond.
1.3 Given that the pI for glycine is 6.1, to which electrode,
positive or negative, will glycine move in an electric
field at pH 2? Explain.
Correct answer = D. The two cysteine residues
can, under oxidizing conditions, form a disulfide
bond. Glutamine’s 3-letter abbreviation is Gln.
Proline (Pro) contains a secondary amino group.
Only one (Arg) of the seven would have a positively charged side chain at pH 7.
Correct answer = negative electrode. When the
pH is less than the pI, the charge on glycine is
positive because the α-amino group is fully protonated. (Recall that glycine has H as its R
group).